Kikuta Junko, Nagai Yasuhito, Kamagata Koji, Chen Hongkai, Yamada Yuki, Kitagawa Takafumi, Uchida Wataru, Iseki Rinako, Guo Sen, Takabayashi Kaito, Hagiwara Akifumi, Wada Akihiko, Taoka Toshiaki, Kato Tadafumi, Aoki Shigeki
Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan.
J Affect Disord. 2025 Jun 11;389:119686. doi: 10.1016/j.jad.2025.119686.
Patients with bipolar disorder (BD) are highly at risk for dementia and may develop brain atrophy, which is linked to cognitive decline. One possible reason for brain atrophy is cellular damage resulting from waste product accumulation caused by glymphatic dysfunction. This study evaluated the glymphatic system in patients with BD, using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and choroid plexus volume (CPV) in two separate BD cohorts. The insight into whether these clearance indices were associated with brain atrophy was also investigated.
The discovery cohort consisted of 28 patients with BD and 28 healthy controls (HCs). The validation cohort included 42 patients with BD and 42 HCs. BD group and HCs in both cohorts underwent group comparisons of the ALPS index, CPV relative to the total intracranial volume (CPV/TIV), and brain gray matter volume. The relationships between the ALPS index and frontal pole volume were determined.
The ALPS index decreased in BD group compared with that in HCs in both cohorts (p < 0.05). While BD group showed increased CPV/TIV and frontal pole atrophy in the discovery cohort, such increase was insignificant in the validation cohort. In the discovery cohort, frontal pole atrophy was related to the ALPS index decrement (r = 0.34, p = 0.02), and the ALPS index-mediated frontal pole atrophy was associated with BD.
Middle-aged patients with BD may experience dysfunction in the excretory pathway of the perivascular space around the medullary veins, likely contributing to frontal pole atrophy.
双相情感障碍（BD）患者患痴呆症的风险极高，且可能出现脑萎缩，这与认知能力下降有关。脑萎缩的一个可能原因是由于脑淋巴系统功能障碍导致废物积累引起的细胞损伤。本研究使用沿血管周围间隙的扩散张量图像分析（DTI-ALPS）和脉络丛体积（CPV），在两个独立的BD队列中评估了BD患者的脑淋巴系统。还研究了这些清除指标是否与脑萎缩相关。
发现队列包括28例BD患者和28例健康对照（HCs）。验证队列包括42例BD患者和42例HCs。两个队列中的BD组和HCs均进行了ALPS指数、相对于总颅内体积的CPV（CPV/TIV）和脑灰质体积的组间比较。确定了ALPS指数与额极体积之间的关系。
两个队列中，BD组的ALPS指数均低于HCs（p < 0.05）。虽然在发现队列中BD组的CPV/TIV增加且额极萎缩，但在验证队列中这种增加并不显著。在发现队列中，额极萎缩与ALPS指数降低有关（r = 0.34，p = 0.02），且ALPS指数介导的额极萎缩与BD相关。
中年BD患者可能存在髓静脉周围血管周围间隙排泄途径功能障碍，这可能导致额极萎缩。
